Synthesis, separation, and theoretical studies of chiral biphenyl lignans (α- and β-DDB)

Two biphenyl lignans, alpha- and beta-DDB (1 and 2, respectively) were efficiently synthesized without contamination by other regio-isomers. The different yields of the Ullmann coupling reactions for the synthesis of 1 and 2 were rationalized by calculating steric hindrance, stability, entropy change, and heat-of-formation values. The enantiomers of 1 and 2 were readily separated by HPLC on a chiral stationary phase. Their configurations were assigned based on the Cotton effect of the authentic natural products.